Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults

Jun Yuan, Steve Pedrini, Rohith Thota, James Doecke, Pratishtha Chatterjee, Hamid R. Sohrabi, Charlotte E. Teunissen, Inge M. W. Verberk, Erik Stoops, Hugo Vanderstichele, Bruno P. Meloni, Christopher Mitchell, Stephanie Rainey-Smith, Kathryn Goozee, Andrew Chi Pang Tai, Nicholas Ashton, Henrik Zetterberg, Kaj Blennow, Junjie Gao, Delin LiuFrank Mastaglia, Charles Inderjeeth, Minghao Zheng, Ralph N. Martins

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Osteoporosis and Alzheimer's disease (AD) mainly affect older individuals, and the possibility of an underlying link contributing to their shared epidemiological features has rarely been investigated. In the current study, we investigated the association between levels of plasma sclerostin (SOST), a protein primarily produced by bone, and brain amyloid-beta (A ss) load, a pathological hallmark of AD. The study enrolled participants meeting a set of screening inclusion and exclusion criteria and were stratified into A ss(n = 65) and A ss+ (n = 35) according to their brain A ss load assessed using A ss-PET (positron emission tomography) imaging. Plasma SOST levels, apolipoprotein E gene (APOE) genotype and several putative AD blood-biomarkers including A ss 40, A ss 42, A ss 42/A ss 40, neurofilament light (NFL), glial fibrillary acidic protein (GFAP), total tau (t-tau) and phosphorylated tau (p-tau181 and p-tau231) were detected and compared. It was found that plasma SOST levels were significantly higher in the A ss+ group (71.49 +/- 25.00 pmol/L) compared with the A ss- group (56.51 +/- 22.14 pmol/L) (P < 0.01). Moreover, Spearman's correlation analysis showed that plasma SOST concentrations were positively correlated with brain A ss load (. = 0.321, P = 0.001). Importantly, plasma SOST combined with A ss 42/A ss 40 ratio significantly increased the area under the curve (AUC) when compared with using A ss 42/A ss 40 ratio alone (AUC = 0.768 vs 0.669, P = 0.027). In conclusion, plasma SOST levels are elevated in cognitively unimpaired older adults at high risk of AD and SOST could complement existing plasma biomarkers to assist in the detection of preclinical AD.
Original languageEnglish
Article number17
Number of pages8
Journalnpj aging
Issue number1
Early online date4 Sept 2023
Publication statusPublished - Dec 2023

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